DESCRIPTION (Applicant's Description): The objective of this Training Program is to produce scientists qualified to make original research contributions in the chemical sciences related to the prevention and treatment of cancer. Eleven faculty members of the Chemistry Department constitute the core research team around which the educational offerings of the program are built. Predoctoral candidates admitted to the program first complete a rigorous selection of courses and examinations after which they concentrate in one of several available research areas, also available to postdoctoral trainees, for their Ph.D. dissertation. Included in this offering are projects in the molecular basis of carcinogenesis, mechanistic studies of anticancer drugs, the synthesis of new antitumor agents, and chemical approaches to the function of biological membranes. Specific projects include studies of cellular responses of DNA damage, the mechanism of platinum anticancer drugs, DNA damage and genetic changes in carcinogenesis, cancer etiology and xenobiotic metabolism, mechanisms of radical-mediated DNA degradation employed by antitumor antibiotics, the principles of molecular recognition to design new antitumor drugs, use of prenyl groups as modulators of signal transduction, interception of cellular events leading to the tumor state, development of new analytical methods to measure environmental carcinogens, and elucidation of signal transduction as mediated by transmembrane proteins. Several synthetic projects include the synthesis of antitumor and tumor-promoting natural products and analogs, the preparation of complex carboaromatic and heteroaromatic compounds exhibiting antitumor activity, the use of catalytic antibodies in synthesis of antitumor target molecules, and the development of mechanism based inhibitors of the diiron center in ribonucleotide reductase. In addition to their research, graduate and postdoctoral students in the program are required to expand their knowledge through participation in a regularly scheduled seminar program and by travel to key scientific meetings. At MIT, trainees present their research results, listen to presentations by their colleagues, and hear a variety of lectures by cancer researchers in the MIT and greater Boston communities. Included in the latter group are epidemiologists and clinical oncologists as well as basic scientists. These seminars give the trainees a comprehensive picture of the roles of environmental factors in the etiology of cancer and of chemotherapy in the clinical management of the disease. Subgroup meetings to discuss research and advise students are also held regularly. At national and international meetings, members of the training grant give papers and attend sessions on work related to their own project as well as the projects of others on the training grant. They then relate their experiences to other trainees in the program upon returning to MIT. Education in the proper conduct of science and in scientific ethics is required through assigned readings and participation in regularly scheduled sessions with the faculty in which case studies are presented and discussed. Apart from their interactions at the regularly scheduled training grant seminars, students and faculty in the program have many formal research collaborations. In addition, there is both formal and informal cooperation among trainees and other MIT cancer research laborato- ries, including those in the Center of Cancer Research, the Toxicology Division, and the Whitehead Institute.